Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns

Abstract

PurposeAsthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year.MethodsSerial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods.ResultsTrajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations.ConclusionsTrajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.

Machine learning-derived asthma phenotypes in a representative Swedish adult population

“…Our second phenotype (Cluster 2) that was characterized by female dominance and early adult-onset asthma with high breathlessness and moderate symptoms, nearly normal lung function, and moderate healthcare use also closely aligns with findings from previous studies 22,26,29,[33][34][35] . This phenotype closely mirrors the phenotype identified by Dudchenko et al 36 , which was notably sensitive to weather as a trigger, while our phenotype had exercise and infections as important triggers.…”

A Systematic Review of Asthma Phenotypes Derived by Data-Driven Methods

“…All the 68 studies [ 8 , 9 , 10 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 …”

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission

“…Although we are not aware of the potential mechanism explaining the double gap we found on FEV1 improvement in remittent vs non-remittent patients, it has been reported that blood and sputum eosinophilia could play a role determining lung function trajectory. Patients with a lower sputum eosinophilia, along with a more pronounced neutrophilic airway inflammation, tend to have a worse FEV1 trajectory, while those with a marked blood and sputum eosinophilia have a fast and sustained improvement in lung function ( 24 ). Moreover, we cannot also exclude that a certain degree of airway remodeling or the impact of comorbidities in non-remittent patients could have influenced the FEV1 improvement with anti IL5/IL5r therapy.…”